Two Genetic Mutations Linked to Tumor Behavior in Thyroid Cancer Patients

DNA flaw
DNA flaw
CDC27 mutations may be associated with less aggressive behavior while SLC25A5 mutations may be associated with more aggressive behavior in papillary thyroid carcinomas.

Researchers have identified 2 new genetic mutations associated with thyroid cancer. They performed whole exome sequencing and IBM Watson analysis on blood and tissue samples and found potential actionable mutations. Their findings indicate that CDC27 gene mutations may be associated with less aggressive behavior and SLC25A5 mutations may be associated with more aggressive behavior.

Kajalben Buddhdev, MD, and colleagues from University of Nebraska Medical Center in Omaha, sequenced the genes expressed in blood and tissue samples from patients with T1A papillary thyroid carcinoma to identify new mutations associated with more aggressive tumor behavior. In the presentation of their data at the 86th Annual Meeting of the American Thyroid Association, they identify 2 novel germline mutations. They were identified as SLC25A5 in 3 of 4 N1b BRAFV600E-positive tumors and CDC27 in 2 of 5 N0 tumors. The researchers report that CDC27 may be a potential germline mutation.

“We did find 2 novel mutations,” said Dr Buddhdev, of the University of Nebraska Medical Center. “However, the CDC27 was seen only in N0 tumors. This information may be helpful in the future when trying to predict the aggressiveness of micropapillary thyroid carcinomas.”

Dr Buddhdev said papillary thyroid carcinoma can vary from indolent to aggressive, with some tumors presenting with N1b disease requiring more aggressive therapy. Some of the currently well-known oncogenic mutations associated with aggressive behavior include BRAFV600E, TERT, and TP53. The researchers searched for additional mutations that could be predictive of biologic behavior in T1a tumors.

They performed whole-exome sequencing and IBM Watson analysis on blood and tissue samples from 6 T1aN0, and 6 T1aN1 papillary thyroid carcinomas from the Thyroid Nodule and Thyroid Cancer Collaborative Registry, which resides at the University of Nebraska Medical Center. Inadequate tissue disqualified 2 of the 12 samples. Dr Buddhdev said 10 samples were analyzed (5 of 10 were T1aN0; 4 of 10 were T1aN1b; and  1 of 10 was T1aN1a), and 9 of 10 were from women. The analysis showed that 8 of 10 cases had classic variant of papillary and the remaining 2 had follicular variant of papillary thyroid carcinoma.

In 2of the 5 tumors, no actionable mutations were found, according to Dr Buddhdev. However, BRAFV600E-activating mutations were present in all T1aN1b cases and in 2 of 5 T1aN0 tumors. The analysis showed the T1aN0 BRAFV600E tumors were multifocal.

In addition, it appeared that all of the tumors with BRAFV600E mutations had concurrent actionable mutations. These mutations included PDGFRA, STAT3, ALK, PDGFD, PHLPP2, EPHA2, PIK3CB, INPPL1, EGFR, and STAT3. However, Dr Buddhdev said there did not appear to be a consistent pattern between tumors. It was observed that while STAT3 and BRAFV600E were both present in 2 tumors, the type of mutations were not the same (N1b-activating, N0-inactivating). This scenario was also repeated with ALK and BRAFV600E. Both were present in 2 tumors, but the type of mutations were different (N1b-inactivating, N0-activating).

“It is important to look at this to understand the aggressiveness and clinical relevance of these tumors. This is a very preliminary result so I cannot say anything further at this time,” Dr Buddhdev told Endocrinology Advisor.

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The researchers also found other no actionable mutations. Dr Buddhdev said activating SLC25A5 mutation was shown in 3 of 4 N1b tumors that also all had BRAFV600E mutations. In 2 of 5 T1aN0 tumors, CDC27 mutations were seen and in both cases they were germline mutations. The researchers identified the MUC4 mutation in 2of 4 T1aN1b and 2 of 5 T1aN0 tumors and present in both follicular variant of papillary thyroid carcinoma. 

Dr Buddhdev said the findings with the BRAFV600E mutations were similar to previously published studies and were present in the majority of T1aN1b tumors.

Disclosures: Dr Buddhdev reports no financial relationships or commercial interests.

For more coverage of ATA 2016, click here.


  1. Buddhdev KB, Patel A, Xiao P, Guda C, Baker J, Goldner W. Highlighted Oral Abstract 1. Whole exome sequencing analysis of T1A papillary thyroid carcinoma. Presented at: American Thyroid Association Annual Meeting; September 21-25, 2016; Denver, Colorado.